Ultrasound is a diagnostic imaging technique which provides a number of advantages over other diagnostic methodology. Unlike techniques such as nuclear medicine and X-rays, ultrasound does not expose the patient to potentially harmful exposures of ionizing electron radiation that can potentially damage biological materials, such as DNA, RNA, and proteins. In addition, ultrasound technology is a relatively inexpensive modality when compared to such techniques as computed tomography (CT) or magnetic resonance imaging.
The principle of ultrasound is based upon the fact that sound waves will be differentially reflected off of tissues depending upon the makeup and density of the tissue or vasculature being observed. Depending upon the tissue composition, ultrasound waves will either dissipate by absorption, penetrate through the tissue, or reflect back. Reflection, referred to as back scatter or reflectivity, is the basis for developing an ultrasound image. A transducer, which is typically capable of detecting sound waves in the range of 1 MHz to 10 MHz in clinical settings, is used to sensitively detect the returning sound waves. These waves are then integrated into an image that can be quantitated. The quantitated waves are then converted to an image of the tissue being observed.
Despite technical improvements to the ultrasound modality, the images obtained are still subject to further recfinement, particularly in regards to imaging of the vasculature and tissues that are perfused with a vascular blood supply. Toward that end, contrast agents are typically used to aid in the visualization of the vasculature and vascular-related organs. In particular, microbubbles or vesicles are desirable as contrast agents for ultrasound because the reflection of sound at an interface created at the surface of a vesicle is extremely efficient. It is known to produce suitable contrast agents comprising microbubbles by first placing an aqueous suspension (i.e., a bubble coating agent), preferably comprising lipids, into a vial or container. A gas phase is then introduced above the aqueous suspension phase in the remaining portion, or headspace, of the vial. The vial is then shaken prior to use in order to form the microbubbles. It will be appreciated that, prior to shaking, the vial contains an aqueous suspension phase and a gaseous phase. A wide variety of bubble coating agents may be employed in the aqueous suspension phase. Likewise, a wide variety of different gases may be employed in the gaseous phase. In particular, however, perfluorocarbon gases such as perfluoropropane may be used. See, for example, Unger et al., U.S. Pat. No. 5,769,080, the disclosure of which is hereby incorporated in by reference in its entirety.
In practice, vials containing the aqueous suspension and gas phases are prepared and sealed, significantly before use, for shipment. It would be highly beneficial to provide apparatus and methods for quickly and non-invasively detecting the presence or absence of the gas phase in the headspace of the sealed vial. The apparatus and methods should be able to determine the presence or absence of one or more specific gases, such as perfluorocarbons, including perfluoropropane (PFP), and should be accurate and robust. Further, the apparatus and methods should be practical for a manufacturing application and, in particular, should afford a low cost per analysis, simplicity of use, and a fast sample through-put rate.